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Pharmacokinetics and pharmacodynamics of the enantiomers of warfarin in man
Author(s) -
Breckenridge A.,
Orme M.,
Wesseling H.,
Lewis R. J.,
Gibbons R.
Publication year - 1974
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1974154424
Subject(s) - warfarin , volume of distribution , pharmacodynamics , pharmacokinetics , anticoagulant , dosing , pharmacology , enantiomer , medicine , chemistry , anesthesia , atrial fibrillation , organic chemistry
The rate of elimination, apparent volume of distribution, plasma clearance, and relative anticoagulant potency of the enantiomers of warfarin have been determined in man. In 9 subjects the plasma half‐life (T½) of R warfarin after a single oral dose of 0.5 mg/kg ranged from 19.9 to 69.S hours, and was significantly longer than that of S warfarin, which ranged from 18.0 to 34.1 hours. There was no significant difference in the apparent volume of distribution of the enantiomers, and thus the plasma clearance of R warfarin was significantly less than that of S warfarin. After multiple dosing to steady state, the plasma T% of R warfarin in 8 subjects ranged from 37.4 to 88.6 hours and was significantly longer than that of S warfarin, which ranged from 21.2 to 42.6 hours. The apparent volume of distribution of the enantiomers was the same, and thus the plasma clearance of R was again significantly less than that of S warfarin. The plasma T½ of R but not of S was significantly longer after multiple dosing than after a single dose. The ratio of the steady‐state plasma concentration of R to S warfarin was 3.80 : 1 in 4 patients with the same degree of anticoagulant control. The relative dose requirements of R to S warfarin were 1.5.9 : 1 in these sub;ects. S warfarin is a more potent anticoagulant than R warfarin in man.